The research program of this laboratory centers on the isolation, properties and biological functions of proteins associated with DNA in the chromosomes of higher organisms. Particular emphasis is placed on reactions which modify the structure of histones and other nuclear proteins after their synthesis is completed. Reactions such as acetylation of lysine residues, methylation of lysine and arginine residues, and phosphorylation of serine and threonine residues in the intact polypeptide chains of nucleic acid-binding proteins are believed to play an important role in chromatin assembly and in the control of transcription. The chemical and enzymatic basis of these reactions, and their results in terms of protein-DNA interaction, are major topics of investigation. Current projects based on these aspects of nuclear protein chemistry include: 1) Comparisons of histone acetylation in active and inactive regions of chromatin, and studies of the effects of acetylation on nucleosome structure and susceptibility to nuclease attack. 2) purification and sequence analysis of a new HMG-class protein localized exclusively in avian erythrocytes. 3) Design and synthesis of a transition-state analog to inhibit the phosphorylation of histone H1 by a cyclic AMP-dependent protein kinase. 4) Isolation and characterization of HMGs and other non-histone proteins released from transcriptionally-active chromatin by limited DNAse I digestion, with particular attention to the release of TNP1, a DNA-binding protein in adenocarcinoma nuclei. 5) Analysis of the proteins associated with ribosomal genes in Physarum, measurement of their interactions with restriction fragments of the rDNA satellite, and tests for their localization and release from peak A, a nucleosome subset enriched in rDNA sequences.